Once injected, the in vivo activity of a drug lasts only a short period of time and, for this reason, repeated administration of the drug is required for a long-term treatment. For example, in order to treat hypertension, drugs such as nifedipine should be administered more than 3 times a day.
Accordingly, there have been numerous efforts to develop a sustained-release formulation which can maintain an effective in vivo drug level for more than 24 hours. For instance, Japanese Patent Publication No. 6001716A (1994. Jan. 11) discloses a solid dispersion formulation based on a hydroxypropyl methylcellulose matrix, and European Patent Publication No. 521310A (1993. Jan. 7), a formulation based on a mixture of hydroxypropyl cellulose and hydroxypropyl methylcellulose which is a water-soluble polymer gelation agent. Further, Japanese Patent Publication No. 62077335A (1987. Apr. 9) teaches a gel forming formulation based on carboxyvinyl polymer; Japanese Patent Publication No. 03169814A (1991. Jul. 23), a formulation based on a mixture of a water-soluble polymer such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl pyrrolidone and methylcellulose, and a water insoluble polymer such as microcystal cellulose; and European Patent No. 274176B (1992. May 27), a sustained release formulation based on polyvinyl pyrrolidone. However, these formulations have the drawback that a constant rate of drug release cannot be maintained for more than 24 hours due to the formation of a gel membrane on the outer shell of the formulation, leaving a non-gelated core.
Further, U.S. Pat. Nos. 4,765,989A, 5,208,037A and 5,019,397A report osmotic release control formulations that exhibit a constant rate of drug release rate following zero order kinetics. However, the manufacturing process of such formulations is very complicated and costly, besides the problem that the drug contained therein is not fully bioavailable (John S Grundy and Robert T. Foster, Clin. Pharmacokinet, 30(1): 28-51(1996)).
The present inventors have previously reported that a formulation of a drug prepared by using a monoglyceride gel carrier releases the drug at a constant rate that follows zero order kinetics for 24 hours, when brought into contact with a hydrophilic matrix or a water soluble matrix (Korean Patent No. 10-0216624 (1999. May 31)). However, this formulation is of an erosion type and has the problem of easy degradation by contractive movements of the gastrointestinals.